The project is designed to test an immunological hypothesis of schizophrenia. Based on previous studies, we postulate that the clinical syndrome of schizophrenia is the result of aberrant function of the septal region due to the impairment of synaptic transmission by an antibody to a specific antigen located on the presynaptic and/or postsynaptic membrane. Studies conducted during the first year of this project have shown that functionally active synaptosomes can be isolated from human brain and we are therefore not restricted to use of similar fractions from animal brain in testing our hypothesis. From a practical standpoint, the demonstration of our hypothesis would open the way for development of diagnostic techniques and provide a rationale for exploration of a specific treatment for schizophrenia. Studies during the second year of the project will include more adequate characterization of the immunological properties of the anti-sera to specific subcellular fractions and comparison to the antibody (taraxein) fraction derived from schizophrenic patients; determination of the effect of taraxein on the catecholamine reuptake mechanism of human synaptosomes by comparing activity to that of known immune sera; further characterization of the reuptake mechanisms of the various putative neurotransmitters in discrete areas of the human brain in order to more precisely define (in terms of inhibition kinetics) the effect of immune and schizophrenic sera on this process and to determine if this effect(s) is similar to that produced by the psychotomimetic drugs.